Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis.
The generation of autoantibody and subsequent tissue deposition of immune complexes (IC) is thought to trigger the pathogenic consequences of systemic autoimmune disease. Modulation of the autoantibody response disrupts pathogenesis by preventing the formation of ICs; however, uncoupling IC formation from subsequent inflammatory responses seems unlikely because of the apparent complexity of the IC-triggered inflammatory cascade. However, the disruption of a single gene, which encodes the gamma chain of the Fc receptor, was found to achieve this uncoupling in a spontaneous model of lupus nephritis, the New Zealand Black/New Zealand White (NZB/NZW) mouse. Gamma chain-deficient NZB/NZW mice generated and deposited IC and activated complement, but were protected from severe nephritis, thus defining another potential pathway for therapeutic intervention in autoimmune disease.
Clynes
R
R
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021, USA.
Dumitru
C
C
Ravetch
J V
JV
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology*; D003167:Complement Activation; D003165:Complement System Proteins / Q000032:analysis; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology*; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D017452:Receptors, IgG; D003165:Complement System Proteins